Biology subjects

Roberts, A.

Publications and source records attributed to Roberts, A..

6 recordsLinked to original sources

bioRxiv2018

Response to Shah et al: Using high-resolution variant frequencies empowers clinical genome interpretation and enables investigation of genetic architecture

Main text Main text Supplemental Data description Declaration of Interests Web Resources References Recent work by Shah and colleagues1 demonstrated that many variants in the ClinVar database2 are misclassified, and that disease-specific allele frequency (AF) thresholds can identify wrongly classified alleles by flagging variants that are too prevalent in the population to be causative of rare penetrant disease. While we agree with the main conclusions of this work, the authors compare their AF filtering approach to our recently published method3, concluding that the method we advanced \"may be prone to removing potentially pathogenic variants\". This is incorrect. Here we demonstrate that our approach is robust, and further illustrate the power of di ...

genomics↗

bioRxiv2018

Intentional gestures predict complex sociality in wild chimpanzee

A key challenge for primates is coordinating behavior with conspecifics in large, complex social groups. Gestures play a key role in this process and chimpanzees show considerable flexibility communicating through single gestures, sequences of gestures interspersed with periods of response waiting (persistence) and rapid sequences where gestures are made in quick succession, too rapid for the response waiting to have occurred. Previous studies examined behavioral reactions to single gestures and sequences, but whether this complexity is associated with more complex sociality at the level of the dyad partner and the group as a whole is not well understood. We used social network analysis to examine how the production of single gestures and sequences of gestures was related to the duration of time spent in proximity and individual differences in proximity in wild East African chimpanzees (Pan troglodytes schweinfurthii). Pairs of chimpanzees that spent a longer duration of time in proximity had higher rates of persistence, but not a higher rate of single gesture or rapid sequences. Central individuals in the social network received higher rates of persistence, but not rapid sequence or single gesture. Intentional gestural communication plays an important role in regulating social interactions in complex primate societies.

animal behavior and cognition↗

bioRxiv2018

Genetic potential for disease resistance in a critically endangered frog decimated by chytridiomycosis.

Southern corroboree frogs (Pseudophryne corroboree) have been driven to functional extinction in the wild after the emergence of the amphibian fungal pathogen Batrachochytrium dendrobatidis (Bd) in southeastern Australia in the 1980s. This species is currently maintained in a captive assurance colony and is managed to preserve the genetic diversity of the founding populations. However, it is unlikely that self-sustaining wild populations can be re-established unless Bd resistance increases. We performed a Bd-challenge study to investigate the association between genetic variants of the major histocompatibility complex class IA (MHC) and genome-wide single nucleotide polymorphisms (SNPs). We also investigated differences in Bd susceptibility among individuals and populations, and the genetic diversity and population genetic structure of four natural P. corroboree populations. We found several MHC alleles and SNPs associated with Bd infection load and survival, provide evidence of significant structure among populations, and identified population-level differences in the frequency of influential variants. We also detected evidence of positive selection acting on the MHC and a subset of SNPs as well as evidence of high genetic diversity in P. corroboree populations. We suggest that low interbreeding rates may have contributed to the demise of this species by limiting the spread of Bd resistance genes. However, our findings demonstrate that despite dramatic declines there is potential to restore high levels of genetic diversity in P. corroboree. Additionally, we show that there are immunogenetic differences among captive southern corroboree frogs, which could be manipulated to increase disease resistance and mitigate the key threatening process, chytridiomycosis.

genomics↗

bioRxiv2017

SemEHR: A General-purpose Semantic Search System to Surface Semantic Data from Clinical Notes for Tailored Care, Trial Recruitment and Clinical Research

ObjectiveUnlocking the data contained within both structured and unstructured components of Electronic Health Records (EHRs) has the potential to provide a step change in data available forsecondary research use, generation of actionable medical insights, hospital management and trial recruitment. To achieve this, we implemented SemEHR - a semantic search and analytics, open source tool for EHRs.\n\nMethodsSemEHR implements a generic information extraction (IE) and retrieval infrastructure by identifying contextualised mentions of a wide range of biomedical concepts within EHRs. Natural Language Processing (NLP) annotations are further assembled at patient level and extended with EHR-specific knowledge to generate a timeline for each patient. The semantic data is serviced via ontology-based search and analytics interfaces.\n\nResultsSemEHR has been deployed to a number of UK hospitals including the Clinical Record Interactive Search (CRIS), an anonymised replica of the EHR of the UK South London and Maudsley (SLaM) NHS Foundation Trust, one of Europes largest providers of mental health services. In two CRIS-based studies, SemEHR achieved 93% (Hepatitis C case) and 99% (HIV case) F-Measure results in identifying true positive patients. At Kings College Hospital in London, as part of the CogStack programme (github.com/cogstack), SemEHR is being used to recruit patients into the UK Dept of Health 100k Genome Project (genomicsengland.co.uk). The validation study suggests that the tool can validate previously recruited cases and is very fast in searching phenotypes - time for recruitment criteria checking reduced from days to minutes. Validated on an open intensive care EHR data - MIMICIII, the vital signs extracted by SemEHR can achieve around 97% accuracy.\n\nConclusionResults from the multiple case studies demonstrate SemEHRs efficiency - weeks or months of work can be done within hours or minutes in some cases. SemEHR provides a more comprehensive view of a patient, bringing in more and unexpected insight compared to study-oriented bespoke information extraction systems.\n\nSemEHR is open source available at https://github.com/CogStack/SemEHR.

bioinformatics↗

bioRxiv2017

Mid-Infrared Spectroscopy Study of Effects of Neonicotinoids on Forager Honey Bee (Apis mellifera) Fat Bodies and Their Connection to Colony Collapse Disorder

This study investigated the negative effects of neonicotinoid pesticides on honey bees in environment surrounding areas of pesticide use. The aim of the experiment is to identify possible contributors to the sudden decrease in honey bee population over the past 60 years, a phenomenon known as Colony Collapse Disorder. Analysis was performed on three sets of bees: the control group which was not in contact with pesticides, the infected dead group which was a set of bees suspected to have died due to neonicotinoids, and the infected alive group which was suspected to be under the influence of neonicotinoids. After dissecting the bee samples and extracting their fat bodies, the chemical composition and protein structures of the samples were analyzed using Mid-Infrared Beamline at the Canadian Light Source. Results from the spectra of bee samples exposed to neonicotinoids demonstrated possible residual pesticide chemicals within fat bodies. Several spectral peaks were also correlated with a possible change in protein secondary structures from primarily {beta}-sheet to -helix within fat bodies of neonicotinoid-affected bees. It is likely that the pesticides caused the growth of additional -helical structures, which is consistent with consequences of the inhibition of nicotinic acetylcholine receptors (nAChRs) a current pathway of harm of Colony Collapse Disorder as identified in past literature.

pharmacology and toxicology↗

bioRxiv2017

CogStack - Experiences Of Deploying IntegratedInformation Retrieval And Extraction Services In A Large National Health Service Foundation Trust Hospital

BackgroundTraditional health information systems are generally devised to support clinical data collection at the point of care. However, as the significance of the modern information economy expands in scope and permeates the healthcare domain, there is an increasing urgency for healthcare organisations to offer information systems that address the expectations of clinicians, researchers and the business intelligence community alike. Amongst other emergent requirements, the principal unmet need might be defined as the 3R principle (right data, right place, right time) to address deficiencies in organisational data flow while retaining the strict information governance policies that apply within the UK National Health Service (NHS). Here, we describe our work on creating and deploying a low cost structured and unstructured information retrieval and extraction architecture within Kings College Hospital, the management of governance concerns and the associated use cases and cost saving opportunities that such components present.\n\nResultsTo date, our CogStack architecture has processed over 300 million lines of clinical data, making it available for internal service improvement projects at Kings College London. On generated data designed to simulate real world clinical text, our de-identification algorithm achieved up to 94% precision and up to 96% recall.\n\nConclusionWe describe a toolkit which we feel is of huge value to the UK (and beyond) healthcare community. It is the only open source, easily deployable solution designed for the UK healthcare environment, in a landscape populated by expensive proprietary systems. Solutions such as these provide a crucial foundation for the genomic revolution in medicine.

bioinformatics↗